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Abstract

Introduction Coronary heart disease (CHD) is affected by both genetic and environmental factors. These classes of factors may act independently or interactively (gene-environment interactions). Recent large genome-wide association (GWA) studies have identified several genetic loci associated with CHD. However, few studies have considered the modifying effects of specific environmental factors on these associations, and the full extent of how those environmental factors affect the additive genetic component of CHD is not known.

Methods The environmental factors studied were smoking (ever regular smoker, never regular smoker); alcohol intake (never-drinking, drinking); physical activity (sedentary vs. non-sedentary); and highest BMI during life time (normal [less than 25 kg/m2], overweight [25 to 30 kg/m2], and obesity [more than 30 kg/m2]). All same-sex twins born before 1958 in the Swedish Twin Registry were included in the current study. We identified 6,133 incident CHD events as the first CHD onset without any prior myocardial infarction, stroke or heart failure. We estimated heritability of CHD conditioned on the above-mentioned environmental factors in up to 26,901 twin pairs with environmental information available. Parameter estimation and model fitting was conducted with structural equation modeling as implemented in the software package Mx.

Preliminary results The overall heritability of CHD in our sample was 36% (adjusted for age and sex). Smoking and overweight/obesity significantly modified the additive genetic component of CHD (P<0.001 and P=0.038, respectively). Thus, heritability of CHD differed between smokers (29.0%) and non-smokers (42.5%). Further, heritability of CHD also differed among different categories of BMI: 29.9% among normal-weight, 27.1% among overweight and 23.6% among obese individuals. Neither alcohol consumption nor physical activity had any significant modifying effect on heritability of CHD (P=0.33 and 0.16, respectively)

Conclusion In our nation-wide twin study of 26,901 twin pairs, purported measures of the environment affected heritability of CHD incidence. We demonstrated that smoking, as well as overweight and obesity modify heritability estimates, potentially indicating that genetic factors play a more prominent role for disease development in the absence of important environmental factors. Our results suggest that increased understanding of gene-environment interactions will be important for full understanding of the etiology of CHD.